Hints of Success in Fetal Cell Transplants

April 22, 1999: WASHINGTON -- In a small but well-controlled study using
tissue from aborted fetuses to treat Parkinson's disease, a team of
researchers announced on Wednesday that they have relieved the symptoms of
some patients, a discovery that experts say suggests that scientists are on
the verge of being able to repair the damaged brain.

The study involved only 40 patients, just 20 of whom received the
transplants, and the improvements, while significant, were dramatic in only
a few. It remains to be seen how long they will last. Those who benefited
were better able to move and experienced less stiffness before taking their
daily medication. Some were able to switch to less potent drugs.

But the findings are tentative. And the experiment, the first of its kind,
is certain to inflame a debate that has divided abortion rights advocates
and opponents for more than a decade: the questions of whether fetal tissue
should be used in medical research, and whether taxpayers should pay for it.

For reasons the researchers do not quite understand, they saw the best
results in the nine transplant patients who were younger than 60; older
patients, who account for the majority of those with Parkinson's, were not
helped overall. Some got better but some got worse. The researchers said
there was no way to predict who would benefit.

But despite the small size of the study and its mixed results, experts said
it offered a tantalizing hint that the transplants may someday work. It
found that the fetal cells took hold and established new networks to
produce a missing neurochemical, dopamine, in the brains of two-thirds of
all the transplant recipients, regardless of their age.

"Ten or 15 years ago, people would have thought of this as science
fiction," said Dr. Gerald Fischbach, director of the National Institute of
Neurological Disorder and Stroke, which paid for the study. Given other
promising developments in Parkinson's disease, including research involving
electrical stimulation of the brain, Fischbach predicted that "within the
next 10 years there will be a much more rational and safe and effective
means of reversing the dopamine deficit."

Of the results announced on Wednesday, Fischbach said, "I think they are
extremely promising. My view is that the surgery worked. The cells took.
They survived, they were manufacturing the transmitter dopamine."

Others were not quite so enthusiastic. "It's mixed," said Dr. J. William
Langston, president of the Parkinson's Institute, a nonprofit research
organization in Sunnyvale, Calif. "I'm disappointed that the results were
not more dramatic. On the other hand, they do show that this seems to be
feasible. I think it is a very important first step."

The four-year study, which the government said cost $5.7 million, was led
by Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley
Fahn of Columbia Presbyterian Center in Manhattan. They announced their
findings at a conference of the American Academy of Neurology in Toronto,
11 years after President Reagan first banned taxpayer support for such
experiments and six years after President Clinton lifted that ban.

The results have not yet been published in a peer-reviewed scientific
journal, and in interviews, Freed and Fahn were cautious about their
results. They emphasized that questions about the proper dose of cells, and
why some patients did better than others, must be be answered before fetal
cell transplants can might be put into widespread use.

"We need to reduce the variability of the transplant response," Freed said,
"namely to know predictably how many cells will survive following
transplant and who is the best candidate for a transplant."

More than one million Americans suffer from Parkinson's Disease, a
degenerative neurological condition that slowly strips patients of control
over their own muscles. There is no cure; although the disease can be
treated with medication, primarily the drug leva-dopa, it eventually stops
working. Patients with advanced cases often lose their ability to walk and
speak.

For years, Parkinson's patients have watched, frustrated, as their symptoms
have worsened while the fetal cell research became caught up in abortion
politics. In 1988, Freed began operating on patients with private money,
and he continues to to so, he said, in an effort to refine his technique.
The operations cost about $35,000 apiece; some have been paid for by
patients, some by a Denver philanthropist.

But there were difficulties. The fetal tissue is hard to obtain, a problem
that might prevent the procedure from being used widely. And until he got
government support, Freed said, he was prevented from conducting "a truly
high quality study."

In 1993, when Clinton lifted the funding ban, he teamed up with Fahn to
submit a grant application. The grant was approved the following year, as
was one for another team, led by Dr. C. Warren Olanow of the Mt. Sinai
School of Medicine in New York. Olanow said he will report his results in
two years.

The experiments are controversial on two fronts. Not only have they aroused
the ire of abortion opponents, they have drawn criticism from ethicists who
objected to their placebo-controlled design.

In the Freed-Fahn study, each patient underwent neurosurgery: four tiny
holes, drilled through the wrinkle lines above the eyebrows into the skull,
to clear a pathway to the brain. But only half received injections of
dopamine-producing cells into the putamen, the region of the brain that
controls movement.

In the others, the surgery was a sham, designed to test the placebo
response, in which patients get better simply by thinking they have been
treated. And indeed, the experiment found a particularly powerful placebo
effect in at least three patients in the control group.

"They got this placebo surgery and immediately they felt better," Fahn
said. "And that feeling of getting better lasted an entire year." Others
also responded to the placebo, he said, but for not quite as long.

Among them was Lynda McKenzie, a 46-year-old former crafts shop owner from
outside Toronto who said she was convinced she had had the real surgery for
three or four months after her sham operation. "I felt good afterwards,"
she said. "I was sure I had it."

But the study also left the family of at least one participant feeling
desperate, and betrayed. Jack Celnik, a 63-year-old retired nuclear
physicist from Lakewood, N.J., was among those in the placebo group. Each
was monitored for 13 months and was to be offered the real transplant after
that. But given the study's results, doctors are advising Celnik not to
have the surgery.

"This was like his last hope and his last chance," said his daughter, Gitty
Charnas, in a telephone interview on Wednesday. She spoke at a rapid clip,
the exasperation and anger evident in her voice. "They used him."

Freed said that Celnik's case poses a quandary: Is it proper to perform the
surgery, which poses a small risk of hemorrhage and stroke, on a patient
who is unlikely to benefit from it, even if that patient demands it?

"We pointedly have not operated on any older patients after we became aware
of this result," he said. "We are going to have to have a long talk with
the people at NIH, as well as the patients."

Nineteen women and 21 men enrolled in the trial. The participants had
suffered from Parkinson's Disease for an average of 13.8 years when the
surgeries began in May 1995. Half the participants were older than 60, but
none was older than 75.

As measured on a standard scale that rates Parkinson's symptoms, the
younger patients who received the transplants demonstrated a 30 percent
improvement, Fahn said. They did not relieve the patient's tremors, nor
ease the "freezing phenomenon," in which patients freeze up mid-stride. But
they lessened slowness and stiffness when patients were off their medicine.

Two patients, both older than 60, died of circumstances unrelated to their
transplants, one of a heart attack and the other in a car accident. In both
cases, Freed said, autopsies showed evidence of cell growth in their brains.

By SHERYL GAY STOLBERG
Copyright 1999 The New York Times Company

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